Is BEAM Regimen Augmentation Possible for Relapsed or Refractory Lymphoma?

ROCHESTER, NY-Current strategies using high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) cure less than half of in vivo patients with recurrent or resistant lymphoma, and drug resistance is the usual reason for treatment failure. Attempts to increase the dose of HDC/AHSCT regimens to address this problem have been limited by regimen-related toxicity (RRT) to various organs. Gordon L. Phillips II, MD, director of the Blood and Marrow Transplant and Leukemia Program, Strong Health and James P. Wilmot Cancer Center, Rochester, New York and colleagues from the Medical College of Wisconsin are addressing this problem by assessing whether the cytoprotectant amifostine(Drug information on amifostine) (Ethyol) can reduce RRT to permit augmentation of the widely used BEAM (carmustine [BiCNU], etoposide(Drug information on etoposide) (Ve- Pesid), ara-C [cytarabine; Cytosar- U], melphalan(Drug information on melphalan) [Alkeran]) regimen. "BEAM is the most widely used HDC/AHSCT regimen for lymphoma, with acceptable nonrelapse mortality rates of less than 10%. [In BEAM, melphalan is given at 140 mg/m²]. Toxicity is consid- ered acceptable if mortality rates not due to relapse are less than 10%," Dr. Phillips said. Melphalan Dose Escalation
In other studies, single-agent melphalan doses of 200 to 220 mg/ m² are the highest that can be given-without cytoprotection- owing to mucosal RRT. Adding amifostine can permit increased melphalan doses of 280 mg/m², Dr. Phillips said. "Thus, use of cytoprotectors to minimize RRT of existing regimens might permit dose escalation, which might cure more patients." This concept is being tried in a phase I melphalan dose-escalation study using BEAM in which melphalan is escalated in 20 mg/m² increments in a cohort design. Amifostine was given at 740 mg/m² x 7. Dr. Phillips reported results for four evaluable patients of the six enrolled (four with non- Hodgkin's lymphoma, and two with Hodgkin's lymphoma). ALL (acute lymphoblastic leukemia) engrafted and RRT was not noted at the initial dose level; patient accrual and dose escalation continues. "The need for multiple doses of amifostine was assumed but is not proven," he said. The investigators concluded that multiple-dose amifostine can be given without severe problems but it is unclear if this reduces RRT beyond the melphalan dose level of 140 mg/m².